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MGH

Published On September 28, 2017

TECHNOLOGY

Medicine in the Mix

The science of embedding medications in polymers opens new doors.

A well-designed prosthetic seamlessly replaces bone and tissue. But for prosthetics placed inside the body, matching the real thing can be devilishly difficult. The most common prosthetics are artificial joints, and every year more than one million people in the United States receive manufactured knee and hip joints to replace those ravaged by osteoarthritis. The new parts, made from metal and polyethylene or ceramic components, fail as often as 10% of the time within the first decade of use because of complications such as infections or particles that come loose and inflame surrounding tissues.

A breakthrough for hip and knee joints came in the mid-1990s, with the development of a polyethylene material that didn’t easily break down. Then in 2007, Orhun Muratoglu, director of the Massachusetts General Hospital Harris Orthopaedics Laboratory, found that the substance could be made significantly more durable by soaking it in vitamin E (“Joint Replacement: Forming Stronger Bonds,” MGH Research Issue 2011); this became the joint material most widely used today.

But challenges remain. In one catastrophic complication of total knee and hip replacements, tissue around the artificial joint becomes infected, typically as a result of bacteria entering the wound. Such infections occur in 1% to 2% of people with joint replacements, and oral or intravenous antibiotics don’t help much because of poor blood flow to the area and the tenacity of the bacteria that coat the implant.

“There wasn’t much more we could do to minimize exposure of the wound to bacteria during surgery,” says Muratoglu. “But what if we delivered antibiotics via the implant itself? If the prosthesis could be impregnated with medication, that would prevent bacteria from colonizing around it and on it.”

So Muratoglu and Ebru Oral, associate director of biomaterials in the Harris Lab, came up with a new material that could deliver antibiotics for up to a month. “Four weeks will have protective effects,” says Oral. “But we can also deliver the drug for much longer by changing the concentration of antibiotics,” she adds.

Joints mixed with antibiotics already exist, but they are made of less durable materials and can’t support a patient’s full weight. Current versions are used only temporarily to treat infections, then replaced with a polymer implant. Oral’s material incorporated the antibiotics into the sturdiest polymer in use—Muratoglu’s vitamin E–soaked polyethylene, intended to be used for 10 years or more.

Oral had to contend with the drug’s tendency to form itself into tiny spheres—a shape that causes gaps and pores that weaken structural integrity of the polymer. She found a way to tease the antibiotic molecules into thin, elongated clusters, which allow drug and polymer to connect more seamlessly. Antibiotics are also sensitive to heat and can degrade, so she developed a methodology that limits the drug’s exposure to high heat while turning the polymer into a solid.

So far, the material has been tested on rats and rabbits, and Oral and Muratoglu will soon seek approval from the Food and Drug Administration for its use in permanent prosthetics in humans. They are also looking at other places it might be useful—such as in trauma surgery, where it could stabilize broken bones and decrease the high risk of infection. Oral’s joint has also attracted the attention of the Department of Defense, which will be awarding MGH a $2 million grant for Oral to study how another medication—nonopioid pain relievers—can be incorporated into polyethylene joints and trauma devices.

“Joint replacement surgery is very painful,” says Oral. “If we can deliver analgesics into the joint space via the implant for a couple of weeks after surgery, we may be able to minimize the need to give the patient follow-up narcotics. Fewer prescriptions would mean we’re not fueling the opioid epidemic.”

In the meantime, Muratoglu hopes that this third generation of prosthetic materials from the lab can head off the worst complications of an already painful procedure. “These antibiotic-eluting joints will make a huge difference—a life-or-death difference—to some patients,” he says.